The Action to Control Cardiovascular Risk in Diabetes (ACCORD) is a randomized clinical trial with 3 components, determining the effects of blood glucose lowering, blood pressure lowering, and lowering of serum triglycerides plus raising serum high density lipoprotein cholesterol levels on cardiovascular disease (CVD) in patients with type 2 diabetes. 10,000 participants will be randomly assigned in equal numbers to two glycemic management treatment arms. An intensive treatment arm will aim to achieve and maintain hemoglobin A1C level < 6.0%. A conventional treatment arm will target an A1C range of 7.0-7.9% with an expected mean value of approximately 7.5%. 4,200 of these participants will simultaneously be randomized to one of two hypertension management protocols. The intensive treatment arm targets a systolic blood pressure (SBP) < 120 mmHg and the conventional treatment arm targets a SBP <140 mmHg. 5,800 dyslipidemic ACCORD participants (HDL < 40 mg/dl) will be randomly assigned in a double masked fashion to either a placebo or fenofibrate 160 mg daily for reduction of triglyceride levels and increase in high-density lipoprotein cholesterol levels, after low-density lipoprotein cholesterol has been lowered with statin therapy (simvastatin 20 mg daily) to target LDL levels of approximately 100 mg/dl or lower. The primary endpoint of the ACCORD Trial is death from cardiovascular causes, non-fatal myocardial infarction and non-fatal stroke. Secondary outcomes include: the combination of the primary outcome plus any revascularization for coronary artery disease plus hospitalization for congestive heart failure; total mortality, cardiovascular mortality; any one of the specific coronary heart disease endpoints noted above, and fatal and non-fatal strokes. Other microvascular complications were also assessed in this study. An ancillary eye study was designed to evaluate the effects of these medical treatments on diabetic retinopathy within the ACCORD Trial. The ACCORD Eye Study consists of 2 eye exams with fundus photography of 7 stereoscopic fields, scheduled for baseline and year 4 of follow-up. The projected sample size is 4065 patients. The main ACCORD Trial, which follows the Vanguard Phase, recruited and randomizes participantss from February 2003 through June 2005. The ACCORD Eye Study showed that intensive glycemic control and intensive lipid therapy with fenofibrate and a statin reduced the risk of progression of diabetic retinopathy. At 4 years, the rates of progression of diabetic retinopathy were 7.3% with intensive glycemia treatment, versus 10.4% with standard therapy (adjusted odds ratio, 0.67; 95% confidence interval CI, 0.51 to 0.87; P = 0.003); 6.5% with fenofibrate for intensive dyslipidemia therapy, versus 10.2% with placebo (adjusted odds ratio, 0.60; 95% CI, 0.42 to 0.87; P = 0.006); and 10.4% with intensive blood-pressure therapy, versus 8.8% with standard therapy (adjusted odds ratio: 1.23; 95% CI, 0.84 to 1.79; P = 0.29). ACCORD Eye study participants, who had baseline and year 4 eye exams and fundus photograph, were re-examined in the ACCORD Follow-on (ACCORDION) Eye Study (2010-2014) 4 years following ACCORD trial closeout. The outcome measure was diabetic retinopathy progression of 3 steps on the Early Treatment Diabetic Retinopathy Study scale. Results: Diabetic retinopathy progressed in 5.8% with intensive glycemic treatment versus 12.7% with standard (adjusted odds ratio (aOR): 0.42, 95% confidence interval CI: 0.28 to 0.63, P<0.0001); 7.5% with intensive BP treatment versus 6.0% for standard (aOR: 1.21, 95% CI: 0.61 to 2.40, P=0.59); and 11.8% with fenofibrate versus 10.2% with placebo (aOR: 1.13, 95% CI: 0.71 to 1.79, P=0.60) in ACCORDION Eye participants (n=1310). Conclusions: Prior intensive glycemic control continued to reduce diabetic retinopathy progression, despite similar A1C levels when ACCORD Study ended. This persistence of benefits of glycemic control is demonstrated for the first time study in persons with type 2 diabetes of 10 years duration and established cardiovascular disease, unlike the newly diagnosed participants of UKPDS, that demonstrated this effect. The benefit of fenofibrate, however, did not persist. Intensive BP control had no effect.